Autonomic Dysfunction Related to Postacute SARS-CoV-2 Syndrome.

Persistence of symptoms beyond the initial acute phase of coronavirus disease-2019 (COVID-19) is termed postacute SARS-CoV-2 (PASC) and includes neurologic, autonomic, pulmonary, cardiac, psychiatric, gastrointestinal, and functional impairment. PASC autonomic dysfunction can present with dizziness, tachycardia, sweating, headache, syncope, labile blood pressure, exercise intolerance, and "brain fog." A multidisciplinary team can help manage this complex syndrome with nonpharmacologic and pharmacologic interventions.

Long COVID: Rapid Evidence Review

Postacute sequelae of COVID-19, also known as long COVID, affects approximately 10% to 30% of the hundreds of millions of people who have had acute COVID-19. The Centers for Disease Control and Prevention defines long COVID as the presence of new, returning, or ongoing symptoms associated with acute COVID-19 that persist beyond 28 days. The diagnosis of long COVID can be based on a previous clinical diagnosis of COVID-19 and does not require a prior positive polymerase chain reaction or antigen test result to confirm infection. Patients with long COVID report a broad range of symptoms, including abdominal pain, anosmia, chest pain, cognitive impairment (brain fog), dizziness, dyspnea, fatigue, headache, insomnia, mood changes, palpitations, paresthesias, and postexertional malaise. The presentation is variable, and symptoms can fluctuate or persist and relapse and remit. The diagnostic approach is to differentiate long COVID from acute sequelae of COVID-19, previous comorbidities, unmasking of preexisting health conditions, reinfections, new acute concerns, and complications of prolonged illness, hospitalization, or isolation. Many presenting symptoms of long COVID are commonly seen in a primary care practice, and management can be improved by using established treatment paradigms and supportive care. Although several medications have been suggested for the treatment of fatigue related to long COVID, the evidence for their use is currently lacking. Holistic treatment strategies for long COVID include discussion of pacing and energy conservation;individualized, symptom-guided, phased return to activity programs;maintaining adequate hydration and a healthy diet;and treatment of underlying medical conditions.Copyright © 2022 American Academy of Family Physicians.

A CASE OF POSTURAL ORTHOSTATIC TACHYCARDIA SYNDROME AFTER MRNA COVID-19 VACCINE

CASE: Ms.X is a 31-year-old female with an unremarkable medical history who presented to the general medicine clinic with palpitations that started 3 days after taking her second dose of Pfizer Covid vaccine. The palpitations ocurred exclusively when standing, with no associated chest pain, dizziness, or presyncope. History is negative for tobacco smoking, drug or alcohol use, and consumption of energy or caffeinated beverages. The physical examination was notable for moist mucous membranes and normal volume examination. Orthostatic vitals were remarkable for an increase in HR by 30 beats with minimal change in BP. EKG showed a normal sinus rhythm, and lab workup inclusive of a CBC, CMP, and TSH was unremarkable. As such, the patient was referred for tilt-table testing. Within 8 minutes of upright tilting, HR was137 from a baseline of 77, and BP was 144/108 from 125/71. A looprecorder was inserted which revealed presence of patient triggered episodes of sinus tachycardia upon standing. The patient was started on propranolol 10 mg every 4-6 hours while awake with almost complete resolution of palpitations. IMPACT/DISCUSSION: The incidence of POTS is 0.2-1% in developed countries, with a 5:1 female-male ratio. It presents with orthostatic symptoms like light-headedness, presyncope, and palpitations. It can occasionally present with non-orthostatic symptoms like nausea, bloating, and diarrhea. The pathophysiology is not well-understood but is postulated to be due to an autoimmune disorder, abnormally increased sympathetic activity, and/or sympathetic denervation leading to central hypovolemia and reflex tachycardia. It is a diagnosis of exclusion, but table-tilt test is used to help confirm it. The onset is typically precipitated by immunological stressors like viral infections, vaccination, and pregnancy. Recently, several case reports have been published describing POTS following infection with COVID-19 infection. This was described as long-COVID postural tachycardia syndrome by the American Autonomic Society. However, the association of POTS with COVID-19 vaccine is unclear. Only one case report was published describing the development of POTS after COVID-19 mRNA vaccine. Information relating to this remain limited, and approach to diagnosis and treatment is variable. Our understanding of this condition in relation to vaccination is mostly extrapolated from previously published reports describing it in relation to HPV vaccine. As more people continue to take the vaccine, physicians should be alert to the diagnosis. CONCLUSION: POTS is a frequently underdiagnosed or misdiagnosed disorder. It is characterized by an increase in HR by 30 within 10 minutes of standing . In rare instances, it has been described as a postvaccination adverse immune phenomena, and more recently related to mRNA COVID-19 vaccination. Increased recognition, diagnosis, and reporting will contribute to better understanding and treatment.

COVID-Long Haulers Can Develop POTS (Postural Orthostatic Tachycardia Syndrome) with Small Fiber Neuropathy and Abnormal Autonomic Testing

Objective: A substantial number of COVID long-haulers have developed POTS, which warrants further investigation. This study is intended as a first look at a new and growing patient population that is bringing greater attention to the prevalent autonomic disease of POTS. Background: POTS (Postural Orthostatic Tachycardia Syndrome) is a disorder of autonomic dysregulation involving overactive compensation for postural blood pressure changes. This debilitating syndrome can be associated with small fiber neuropathy and a broad spectrum of autonomic symptoms including palpitations, changes in sweating, and gastrointestinal problems like constipation. Respiratory and gastrointestinal viruses have been known to cause onset of POTS pathophysiology. In approximately 10% of COVID cases, patients experience long-term health effects after the conclusion of their COVID infection. These patients are called COVID “long-haulers.” Design/Methods: We conducted a chart review of 25 Cleveland Clinic post-COVID POTS patients who are mostly female (84%) to learn about this patient population's distribution of top symptoms, comorbidities, autonomic testing, and autonomic questionnaire scores. Top three symptoms were determined based on the physician's note from the patients' initial visit to the Cleveland Clinic Neurology Department. Results: Our chart review revealed a high occurrence of excitatory comorbidities such as chronic migraine (44%) and irritable bowel syndrome (24%). In addition, when assessing patients' top three POTS symptoms, we found that palpitations, fatigue, and dyspnea were affecting patients most. As with POTS in general, autonomic testing outside of tilt table testing (85.7%) shows variable results with QSART (50%), skin punch biopsy (37.5%), deep breathing (14.3%), and Valsalva testing (0%) all showing positivity rates of 50% or less for our patient sample. Conclusions: Post-COVID POTS could be an excitatory process with hyperadrenergic signaling based on the symptoms and comorbidities. We hope that this chart review will be the launching point for future studies aimed at achieving greater understanding of the post-COVID POTS phenomenon.

Orthostatic Intolerance in Adults Reporting Long COVID Symptoms Was Not Associated With Postural Orthostatic Tachycardia Syndrome.

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults reporting long COVID symptoms. Participants underwent a 3-min active stand (AS) with Finapres® NOVA, followed by a 10-min unmedicated 70° head-up tilt test. Eighty-five participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the first minute post-stand (mean HRnadir: 88 vs. 75 bpm, P = 0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR = 1.09, 95% CI: 1.01-1.18, P = 0.027). Twenty-two (26%) participants had initial (iOH) and 5 (6%) classical (cOHAS) orthostatic hypotension, but neither correlated with OIAS. Seventy-one participants proceeded to tilt, of which 28 (39%) had OI during tilt (OItilt). Of the 53 who had a 10-min tilt, 7 (13%) had an HR increase >30 bpm without cOHtilt (2 to HR > 120 bpm), but six did not report OItilt. In conclusion, OIAS was associated with a higher initial HR on AS, which after 1 min equalised with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent (2%). ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).

Prospective analysis of vascular resistance in patients with persistent tachycardia and or dyspnea on exertion in the post acute sequela of covid-19 syndrome

Introduction: The cause of tachycardia and dyspnea on exertion (DOE) in the Post Acute Sequelae CoV-2 syndrome (PASC) has yet to be identified. While endothelial invasion of the virus is well documented, how that might explain PASC is unknown. Hypothesis: Covid induced changes in vascular signaling to autonomic regulatory centers can induce sinus tachycardia and DOE. Methods: In a prospective, observational study, we enrolled 18 PASC patients who reported DOE or inappropriate tachycardia. All patients had normal left ventricular function, CXR, Hgb and thyroid studies. None had preexisting autonomic dysfunction. Vascular resistance was assessed by echocardiographic measurement of aortic-vascular impedance (Zva)=(systolic BP + mean Ao valve gradient)/stroke volume index. Ambulatory heart rate monitoring and head-up tilt table testing (HUTT) were performed. Results: Consecutively enrolled patients (18) were studied (17 females, ages 27 to 64). None had a significant aortic valve gradient. Zva was elevated in 17 of 18 patients. Ambulatory monitoring revealed episodes of symptomatic sinus tachycardia. Higher average daily heart rates correlated significantly with higher Zva levels (fig1). The 14 patients with DOE trended to higher average Zva levels than the 4 patients without dyspnea (4.13 +- 0.85 vs 3.5 +- 0.24, P=0.14). Of the 17 patients who had HUTT, 16 demonstrated patterns of orthostatic intolerance consistent with excess sympathetic tone including both postural orthostatic tachycardia and neurogenic cardiac syncope. Conclusions: PASC associated sinus tachycardia and HUTT abnormalities result from excess sympathetic tone. Covid-19 vascular injury as evidenced by abnormal Zva values may result in abnormal vascular signaling to autonomic regulatory centers. Resultant increases in sympathetic output may produce inappropriate sinus tachycardia, vasomotor dysregulation and DOE via peripheral vasoconstriction.